The author of 《Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated》 were Geraldy, Magalie; Morgen, Michael; Sehr, Peter; Steimbach, Raphael R.; Moi, Davide; Ridinger, Johannes; Oehme, Ina; Witt, Olaf; Malz, Mona; Nogueira, Mauro S.; Koch, Oliver; Gunkel, Nikolas; Miller, Aubry K.. And the article was published in Journal of Medicinal Chemistry in 2019. Formula: C9H19NO4 The author mentioned the following in the article:
The discovery of isoenzyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biol. functions of individual HDACs and for validating HDACs as drug targets. The isoenzyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, the authors found tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. The authors synthesized tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homol. models indicated that a hydrogen-bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, the authors’ data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the tubastatin A scaffold. In the experiment, the researchers used tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6Formula: C9H19NO4)
tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6) belongs to ethers.Oxygen is more electronegative than carbon, thus the alpha hydrogens of ethers are more acidic than those of simple hydrocarbons. They are far less acidic than alpha hydrogens of carbonyl groups (such as in ketones or aldehydes), however. Formula: C9H19NO4
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem